OBJECTIVES: To determine the rate of and identify reasons for discontinuation of entacapone treatment in Parkinson disease patients. METHODS: A retrospective study design was used, including medical record reviews and telephone call to the patient as needed. RESULTS: Two hundred and twenty-two Parkinson disease patients were started on entacapone over a period of 3 years. One hundred and twenty-two patients (56%) had discontinued the medication by the end of the follow up period. Reasons for discontinuation included lack of efficacy (46%), worsening of parkinsonian symptoms (28%), worsened cognition (20%), dyskinesia (17%), nausea (11%), diarrhea (9%), cost (4%), other side effect (8%), and other, non-medication related reasons (19%). Presence of wearing off at the time of initial treatment and male sex were associated with decreased dropout rates, while the presence of orthostatic hypotension increased the likelihood of discontinuation. Patient age, disease duration, Hoehn and Yahr stage, Unified Parkinson's Disease Rating Scale section II score, presence of dementia, hallucinations, dyskinesias, or depression, number of daily L-dopa doses, and concomitant treatment with dopamine agonists did not affect dropout rate. CONCLUSIONS: Lack of efficacy seems to be the main reason for entacapone discontinuation. Male patients with wearing off and no orthostatic hypotension seem to tolerate the medication better. Advanced disease stage, presence of cognitive dysfunction, and presence of dyskinesia should not necessarily preclude patients from being treated with entacapone, when otherwise indicated.